Glucosidase II beta subunit (PRKCSH)

Glucosidase II beta subunit (PRKCSH) is the regulatory subunit of glucosidase II, a key enzyme of the endoplasmic reticulum (ER) quality control system responsible for trimming glucose residues from N-linked oligosaccharides during glycoprotein maturation[1][2][4][5]. PRKCSH ensures proper protein folding by enabling newly synthesized glycoproteins to exit the ER, thus maintaining protein homeostasis. It contains phosphorylation sites, calcium-binding EF-hand domain, and is retained in the ER by a C-terminal HDEL motif. Beyond glycosylation, PRKCSH modulates critical cellular pathways such as the unfolded protein response (selectively activating the IRE1α branch), programmed cell death (autophagy, apoptosis), calcium signaling, vesicle transport, and, per recent findings, anti-tumor immunity by affecting NK and T cell activity[1][2][3][4][6]. Mutations in the PRKCSH gene cause autosomal dominant polycystic liver disease, and its dysregulation is increasingly implicated in tumorigenesis and cancer progression, including regulation of growth factor signaling and metastasis. PRKCSH is not currently a direct therapeutic target of approved drugs, but its pivotal roles in glycan processing, ER stress adaptation, cell signaling, and immune modulation substantiate its potential as a biomarker and target for future therapy in cancer and liver disease[1][2][3][6].

Other names

80K-HHepatocystinProtein kinase C substrate 80K-HGluIIβGIIBG19P1PKCSHVASAP-60AGE-R2GIIbetaGluIIbetaPCLDPCLD1PLD1Protein kinase C substrate 60.1 kDa protein heavy chainAdvanced glycation end-product receptor 2

Not directly targeted by drugs; however, inhibition or loss of PRKCSH function impacts glycoprotein biogenesis, ER protein quality control, and anti-tumor immunity by modulating unfolded protein response (notably IRE1α branch) and cellular growth signaling[1][2][3].