Cell cycle progression protein 1 (CCPG1)

Cell cycle progression protein 1 (CCPG1) is a vertebrate-specific ER membrane protein serving as a bispecific receptor for selective autophagy of the endoplasmic reticulum (ER-phagy)[1][2]. It contains a large ER luminal region (>500 amino acids) harboring multiple highly conserved cargo-interacting regions (CIRs) that enable CCPG1 to recognize and bind aggregation-prone and misfolded ER luminal proteins. Through these domains, CCPG1 directly interacts with ER-localized substrates (e.g., P3H4, 6xIAPP), and with autophagy-related proteins (such as LC3 and FIP200) on the cytoplasmic side, linking targeted cargo recognition to formation and delivery into autophagosomes. CCPG1 expression is upregulated by cellular ER stress and is essential for effective protein quality control, maintaining ER and cellular homeostasis under stress conditions. Loss or dysfunction of CCPG1 impairs selective ER-phagy, leading to accumulation of toxic ER proteins and contributing to various pathologies, including malignancies driven by defective protein degradation. CCPG1 is not currently a direct drug target, but its pathway is under active investigation for understanding and treating diseases of impaired proteostasis or selective autophagy[1][2].

Other names

CCPG1CCPG8CPR8KIAA1254Cell cycle progression restoration protein 8cell cycle progression protein 1cell cycle progression restoration protein 8

Not established for drugs; however, CCPG1 enables cargo-selective ER-phagy by interacting via its cargo-interacting regions (CIRs) with ER luminal proteins and the autophagic membrane[1][2].