The Journal of Clinical Investigation -- New Articles https://www.jci.org/current en-us 2026 The American Society for Clinical Investigation The Journal of Clinical Investigation http://www.jci.org/assets/common/jci-only-white-blue-bg.png http://www.jci.org <![CDATA[HSD3B1 links ileal steroid metabolism to bile acid regulation in patients with prostate cancer]]> https://www.jci.org/articles/view/202725 info:doi/10.1172/JCI202725 The American Society for Clinical Investigation <![CDATA[Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2]]> https://www.jci.org/articles/view/173913 info:doi/10.1172/JCI173913 The American Society for Clinical Investigation <![CDATA[Oligodendrocyte dysfunction contributes to motor deficits and Purkinje cell axonopathy in spinocerebellar ataxia type 1]]> https://www.jci.org/articles/view/195723 info:doi/10.1172/JCI195723 The American Society for Clinical Investigation <![CDATA[Divergent macrophage-regulated T cell states determine response to Bacillus Calmette-Guérin vaccine in high-risk bladder cancer]]> https://www.jci.org/articles/view/200442 info:doi/10.1172/JCI200442 The American Society for Clinical Investigation <![CDATA[Redirection of sphingolipid metabolism drives cytoskeletal defects in SPLIS and reveals ROCK inhibition as therapy]]> https://www.jci.org/articles/view/194427 A (p.Ser362Thr) SGPL1 variant and analyzed the metabolic and cellular consequences of SPL deficiency, using patient fibroblasts, SGPL1-KO HEK293T cells, and Sgpl1–/– and Sgpl1rosa+fl/fl mice. Metabolic stable isotope labeling revealed that SPL deficiency does not invariably result in S1P accumulation. Instead, SPL-deficient cells maintain near-normal S1P levels through (a) feedback regulation of de novo sphingolipid synthesis via the ORMDL–ceramide axis and (b) increased diversion of excess ceramides into glycosphingolipids. However, perturbation of sphingolipid homeostasis, either by exogenous sphingolipid load or disruption of compensatory regulation, induces pathological intracellular S1P accumulation. In vivo, Sgpl1–/– mice had pronounced urinary S1P excretion and renal S1P enrichment, accompanied by cytoskeletal disorganization and impaired epithelial morphogenesis. Mechanistically, we identify aberrant Rho/ROCK signaling as a key mediator of S1P-driven cytoskeletal dysregulation. Pharmacological ROCK inhibition with fasudil mitigated renal cytoskeletal defects in Sgpl1–/– and Sgpl1rosa+fl/fl mice and partially restored epithelial architecture. These findings redefine the metabolic consequences of SPL deficiency and identify S1P-driven Rho/ROCK hyperactivation as a tractable therapeutic target in SPLIS.]]> info:doi/10.1172/JCI194427 The American Society for Clinical Investigation <![CDATA[Tumor-derived cell-free DNA detected in cerebrospinal fluid enables minimally invasive profiling of pediatric brain tumors]]> https://www.jci.org/articles/view/197391 info:doi/10.1172/JCI197391 The American Society for Clinical Investigation <![CDATA[Immune responses in aging adults]]> https://www.jci.org/articles/view/206227 info:doi/10.1172/JCI206227 The American Society for Clinical Investigation <![CDATA[MVA.HIVconsvX vaccination–evoked T cell expansion inversely associates with age in people with HIV-1 on antiretroviral therapy]]> https://www.jci.org/articles/view/193547 info:doi/10.1172/JCI193547 The American Society for Clinical Investigation <![CDATA[Rewriting the cancer proteome: targeting selective translation as a therapeutic frontier]]> https://www.jci.org/articles/view/207335 info:doi/10.1172/JCI207335 The American Society for Clinical Investigation <![CDATA[Therapeutic targeting of the eIF4E cap-binding domain reveals control of lineage fate in prostate cancer]]> https://www.jci.org/articles/view/199838 info:doi/10.1172/JCI199838 The American Society for Clinical Investigation <![CDATA[Functional, molecular, and digital measurements of biological age]]> https://www.jci.org/articles/view/205777 info:doi/10.1172/JCI205777 The American Society for Clinical Investigation <![CDATA[Chronotherapy to reinforce circadian rhythms improves poststroke outcomes and glymphatic function in mice]]> https://www.jci.org/articles/view/201800 info:doi/10.1172/JCI201800 The American Society for Clinical Investigation <![CDATA[Beyond neuronal degeneration: oligodendroglial dysfunction as a driver of spinocerebellar ataxia type 1 pathogenesis]]> https://www.jci.org/articles/view/209207 info:doi/10.1172/JCI209207 The American Society for Clinical Investigation <![CDATA[GPR182 and the reframing of lacteal chylomicron uptake]]> https://www.jci.org/articles/view/207115 info:doi/10.1172/JCI207115 The American Society for Clinical Investigation <![CDATA[Macropinocytosis inhibition attenuates profibrotic responses in lung fibroblasts and pulmonary fibrosis models]]> https://www.jci.org/articles/view/197651 info:doi/10.1172/JCI197651 The American Society for Clinical Investigation <![CDATA[A tribute to Eugene Braunwald (1929–2026)]]> https://www.jci.org/articles/view/208900 info:doi/10.1172/JCI208900 The American Society for Clinical Investigation <![CDATA[Lipoprotein(a)-associated proteomic signature predicts cardiovascular disease in young adults]]> https://www.jci.org/articles/view/204287 info:doi/10.1172/JCI204287 The American Society for Clinical Investigation <![CDATA[Erratum to Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy]]> https://www.jci.org/articles/view/208844 info:doi/10.1172/JCI208844 The American Society for Clinical Investigation <![CDATA[Joseph C. Wu receives the 2026 ASCI/Stanley J. Korsmeyer Award]]> https://www.jci.org/articles/view/209203 info:doi/10.1172/JCI209203 The American Society for Clinical Investigation <![CDATA[GPR182 is a lipoprotein receptor for dietary fat absorption]]> https://www.jci.org/articles/view/200857 info:doi/10.1172/JCI200857 The American Society for Clinical Investigation <![CDATA[Hyperglycemia aggravates vitiligo through succinate/SUCNR1-mediated T cell activation]]> https://www.jci.org/articles/view/200316 info:doi/10.1172/JCI200316 The American Society for Clinical Investigation <![CDATA[HER2 deficiency causes a developmental disorder with growth retardation and craniofacial malformations]]> https://www.jci.org/articles/view/199043 info:doi/10.1172/JCI199043 The American Society for Clinical Investigation <![CDATA[Activation of the impaired NAMPT/SIRT7/SOD2 axis restores alveolar progenitor cell renewal in idiopathic pulmonary fibrosis]]> https://www.jci.org/articles/view/198031 info:doi/10.1172/JCI198031 The American Society for Clinical Investigation <![CDATA[Skin-resident Langerhans cells drive neuropathic pain via chemokine-dependent neuron-immune communication]]> https://www.jci.org/articles/view/192328 info:doi/10.1172/JCI192328 The American Society for Clinical Investigation <![CDATA[Bittersweet: how hyperglycemia exacerbates vitiligo progression through the succinate/SUCNR1 axis]]> https://www.jci.org/articles/view/207416 info:doi/10.1172/JCI207416 The American Society for Clinical Investigation <![CDATA[The N-terminus of apolipoprotein B mediates the interaction of atherogenic lipoproteins with endothelial cells]]> https://www.jci.org/articles/view/190513 info:doi/10.1172/JCI190513 The American Society for Clinical Investigation <![CDATA[Host-directed immune therapies: a second front in the battle against sepsis]]> https://www.jci.org/articles/view/204736 info:doi/10.1172/JCI204736 The American Society for Clinical Investigation <![CDATA[The EGFR regulates bacterial clearance in cystic fibrosis airway neutrophils]]> https://www.jci.org/articles/view/198292 info:doi/10.1172/JCI198292 The American Society for Clinical Investigation <![CDATA[DYRK1A enhances antitumor immunity in type 1 conventional dendritic cells via mTORC1 activation]]> https://www.jci.org/articles/view/199108 info:doi/10.1172/JCI199108 The American Society for Clinical Investigation <![CDATA[Polyendocrine metabolic ovarian syndrome (PMOS)/polycystic ovary syndrome (PCOS): current and future trends]]> https://www.jci.org/articles/view/202824 info:doi/10.1172/JCI202824 The American Society for Clinical Investigation <![CDATA[Aging reprograms microglia toward an inflammasome-linked response to traumatic brain injury]]> https://www.jci.org/articles/view/207022 info:doi/10.1172/JCI207022 The American Society for Clinical Investigation <![CDATA[Iron overload in steatotic hepatocytes drives systemic metabolic dysfunction via alterations in hepatokine production]]> https://www.jci.org/articles/view/196374 info:doi/10.1172/JCI196374 The American Society for Clinical Investigation <![CDATA[Aging-dependent microglial heterogeneity worsens outcomes in models of traumatic brain injury]]> https://www.jci.org/articles/view/196112 info:doi/10.1172/JCI196112 The American Society for Clinical Investigation <![CDATA[Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling]]> https://www.jci.org/articles/view/190552 info:doi/10.1172/JCI190552 The American Society for Clinical Investigation