Calcium-binding and coiled-coil domain-containing protein 2 (CALCOCO2)

Calcium-binding and coiled-coil domain-containing protein 2 (CALCOCO2, also known as NDP52) is a soluble, cytoplasmic and nuclear multifunctional selective autophagy receptor that recognizes and binds ubiquitinated cargo—such as pathogens, damaged mitochondria, or protein aggregates—and bridges them to the autophagy machinery (notably LC3/GABARAP proteins) for lysosomal degradation[1][3][5][6]. CALCOCO2 is central to mitophagy (Clearance of damaged mitochondria), xenophagy (elimination of pathogens), and aggrephagy (removal of aggregates). It also negatively regulates the NF-κB pathway and is involved in "adaptophagy" (removal of signaling adapter proteins involved in innate immunity), impacting inflammation and cell survival[1]. Nuclear pools of CALCOCO2 interact with RNA polymerase II and chromatin, influencing gene transcription and nuclear organization. Disease-linked variants highlight its importance in inflammation, infection, autoimmunity, neurodegeneration, and potentially as a therapeutic target[1][3][4][5][7].

Other names

NDP52Nuclear domain 10 protein 52Antigen nuclear dot 52 kDa proteinNuclear dot protein 52MGC17318nuclear domain 10 protein NDP52calcium-binding and coiled-coil domain 2

No drugs directly target CALCOCO2, but its mechanism in selective autophagy involves recognizing ubiquitinated cargo, scaffolding autophagy machinery (LC3 family proteins), mediating removal of pathogens and damaged organelles, and regulating immune signaling pathways[1][3][5][6].