DNAJC22 is an Hsp40 co-chaperone family member that functions as a molecular chaperone involved in protein binding and membrane localization 1. The protein is evolutionarily conserved, with mammalian DNAJC22 serving as an ortholog of the Drosophila Wurst protein, a J-domain transmembrane protein essential for clathrin-mediated endocytosis 2. Transcriptional regulation of DNAJC22 is controlled by the hepatocyte nuclear factor Hnf4a, as demonstrated through cross-species computational and experimental validation 3. DNAJC22 has significant disease relevance in neurological and cancer conditions. Genome-wide genetic analysis identified suggestive associations between rare variants in DNAJC22 and Parkinson's disease, particularly in sporadic late-onset PD 4. Additionally, DNAJC22 was identified as a characteristic gene in thyroid cancer pathogenesis, potentially contributing to disease through immune pathway regulation 5. At the molecular evolution level, DNAJC22 shows positive selection signals in Chinese rhesus macaques, enabling rapid temperature regulation and cold adaptation—a mechanism paralleling human northward migration 6. During HIV-1 infection, DNAJC22 appears to positively regulate virus replication 7, though its specific mechanistic role requires further investigation.