Protein phosphatase Slingshot homolog 2

SSH2 (Slingshot homolog 2) is a protein phosphatase that regulates actin filament dynamics by dephosphorylating and activating cofilin, an actin-binding protein that promotes filament disassembly (UniProt: Q76I76). The enzyme also dephosphorylates and inactivates LIMK1, a cofilin kinase, thereby coordinating control of the actin cytoskeleton. Beyond its cytoskeletal role, SSH2 is involved in spermatogenesis and acrosome biogenesis through cofilin-mediated actin remodeling.

SSH2 is broadly expressed across tissues where cytoskeletal dynamics are critical, including the nervous system. No disease associations are documented in UniProt for this protein.

SSH2 is downregulated in Alzheimer's Disease brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log₂ fold-change is −0.67, indicating reduced protein abundance across examined subcellular fractions (P2, P3, S2, S3) in post-mortem AD brain samples by TMT-labeled proteomics. This downregulation may reflect altered actin dynamics and cytoskeletal remodeling in AD neurodegeneration.