What are KASH proteins? KASH proteins (Klarsicht, ANC-1, Syne homology) are C-tail-anchored membrane proteins, which are targeted specifically to the outer membrane of the nuclear envelope. The defining feature of KASH proteins is the carboxy-terminal KASH domain that consists of a hydrophobic region spanning the outer nuclear membrane and 6–30 residues in the perinuclear space. The perinuclear domains of KASH proteins are often highly similar; for example, 13 of 20 residues are identical between Caenorhabditis elegans ANC-1 and human Syne/Nesprin-1 and-2. Other KASH proteins have shorter and/or divergent perinuclear sequences. Due to a lack of homology, additional KASH proteins likely remain to be discovered. KASH proteins also have large, non-conserved cytoplasmic domains.