Protein phosphatase 1 regulatory subunit 15B (PPP1R15B)

Protein phosphatase 1 regulatory subunit 15B (PPP1R15B) is a regulatory subunit that associates with the catalytic subunit of protein phosphatase 1 (PP1) to form a complex responsible for the dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α), thus modulating protein synthesis, particularly under cellular stress conditions[1][5]. This regulation is critical for maintaining protein translation homeostasis, with stress-induced changes leading to a feedback loop for translation recovery. PPP1R15B also has roles independent of translation, such as in membrane trafficking and exocytosis. Genetic variants in PPP1R15B cause syndromes characterized by microcephaly, short stature, and metabolic defects. PPP1R15B is emerging as a cancer vulnerability in multiple myeloma, where its inhibition can activate stress pathways and synergize with anticancer agents[3].

Other names

FLJ14744CREPMSSGM2protein phosphatase 1 regulatory subunit 15Bprotein phosphatase 1, regulatory (inhibitor) subunit 15BPPP1R15B

Inhibition of PPP1R15B increases phosphorylation of eIF2α, driving activation of pro-apoptotic stress response pathways (such as eIF2α-ATF4-CHOP) and suppressing protein synthesis[3][5].