CALCOCO2 (NDP52) is a xenophagy-specific autophagy receptor essential for intracellular bacterial degradation. As an effector of galectin-sensed membrane damage, CALCOCO2 restricts pathogen proliferation by targeting bacteria such as Salmonella typhimurium to autophagosomes through interaction with MAP1LC3A, MAP1LC3B, and GABARAPL2 1. CALCOCO2 orchestrates two distinct phases of xenophagy: initial bacteria targeting to autophagosomes and subsequent regulation of pathogen-containing autophagosome maturation, the latter requiring interaction with MAP1LC3C 23. Beyond xenophagy, CALCOCO2 functions as a primary autophagy receptor for mitophagy, the selective removal of damaged mitochondria. PINK1 recruits CALCOCO2 directly to mitochondria independently of parkin to activate mitophagy, positioning it upstream of LC3 recruitment 4. CALCOCO2 is subject to post-translational acetylation regulation, a mechanism controlling autophagy at multiple levels including cargo assembly and autophagosome-lysosome fusion 5. CALCOCO2 dysfunction is implicated in multiple diseases. In inflammatory bowel disease pathogenesis, autophagy gene alterations including CALCOCO2 disrupt intestinal homeostasis and antimicrobial responses 6. During chr17 obstructive pulmonary disease progression, impaired mitophagy involving CALCOCO2-mediated pathways contributes to mitochondrial damage accumulation and cellular senescence 7. Additionally, CALCOCO2 plays roles in age-related macular degeneration pathology and coronavirus-host interactions 89, establishing its broad clinical relevance in inflammatory and infectious diseases.