Protein phosphatase Slingshot homolog 2 (SSH2) (SSH2)

Protein phosphatase Slingshot homolog 2 (SSH2) is a specialized protein phosphatase that serves as a key regulator of the actin cytoskeleton by specifically dephosphorylating and activating cofilin (UniProt: P59351). This activation allows cofilin to sever and depolymerize actin filaments, a process essential for cell motility, cytokinesis, and neurite outgrowth (PubMed: 12522167). In oncology, SSH2 is frequently upregulated, facilitating the invasive and metastatic capabilities of cancer cells by promoting rapid actin remodeling (PubMed: 24631564). Beyond cancer, SSH2 dysfunction is linked to neurodegenerative pathologies, such as Alzheimer's disease, where aberrant cofilin activity leads to the formation of toxic cofilin-actin rods (PubMed: 21450870). Although no small-molecule inhibitors of SSH2 have reached clinical trials, the enzyme is an attractive target for therapeutic intervention in metastatic cancers and neurodegeneration. Research into SSH2 inhibitors, such as certain sennosides, highlights the potential for modulating this pathway to control pathological cell migration (PubMed: 25447583). The enzyme's role in fundamental cellular processes suggests that therapeutic targeting must be carefully managed to avoid disrupting normal cytoskeletal functions in healthy tissues.

Other names

Slingshot-2SSH-2SSH-2LhSSH-2LSlingshot homolog 2

SSH2 acts by dephosphorylating cofilin at its Ser-3 residue, which converts the inactive phosphorylated form of cofilin into its active state, thereby promoting actin filament severing and depolymerization (PubMed: 12522167).