Protein phosphatase Slingshot homolog 1

SSH1 (protein phosphatase Slingshot homolog 1) is a serine/threonine protein phosphatase that regulates actin filament dynamics by dephosphorylating and activating cofilin, an actin-binding protein that promotes filament disassembly (UniProt: Q8WYL5). The protein also dephosphorylates and inactivates LIMK1, a kinase that inhibits cofilin, thereby modulating the balance of actin polymerization and depolymerization. This function is critical for cellular processes requiring dynamic cytoskeletal remodeling, including neuronal morphogenesis and synaptic plasticity.

SSH1 is implicated in Alzheimer's disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, SSH1 is downregulated (mean log2 fold-change −0.40) based on TMT-labeled proteomic profiling across subcellular fractions (Chaparral AD proteomics). The reduction in SSH1 levels may impair cofilin-mediated actin dynamics, potentially contributing to neuronal cytoskeletal abnormalities and synaptic dysfunction characteristic of AD neurodegeneration.