CLEC16A encodes a C-type lectin domain-containing protein that serves as a critical regulator of cellular quality control processes, particularly mitophagy and autophagy 1. The protein functions as an E3 ubiquitin ligase that modulates mitochondrial health through upstream regulation of the RNF41/NRDP1-PRKN pathway, which controls autophagosome-lysosome fusion during late mitophagy 2. CLEC16A localizes to early endosomes and interacts with retromer complex components and TRIM27, regulating endosomal trafficking and vesicle sorting 3. A disease-associated C-terminal intrinsically disordered protein region is essential for CLEC16A stability and mitochondrial quality control function 2. The protein plays important roles in immune regulation, with overexpression reducing NK cell cytotoxicity and altering dendritic cell maturation, while knockdown increases cytotoxicity and disrupts mitophagy 4. In thymic epithelial cells, CLEC16A modulates autophagy processes that influence T cell selection 5. Disease associations include multiple autoimmune disorders such as type 1 diabetes, multiple sclerosis, and common variable immunodeficiency disorder 67. Loss of CLEC16A function leads to impaired mitophagy, mitochondrial dysfunction, increased neuroinflammation, and severe neurodevelopmental abnormalities 13.