DNAJB12 is a transmembrane endoplasmic reticulum (ER) protein that functions as a co-chaperone for Hsc70/Hsp70 heat shock proteins 1. Its primary function involves protein quality control and membrane protein triage, cooperating with cytosolic Hsp70 on the ER's cytoplasmic face to determine whether nascent polytopic membrane proteins undergo folding or degradation 2. Mechanistically, DNAJB12 uses its cytosolically localized J-domain to bind HSC70 and SGTA, facilitating the reflux of ER proteins to the cytosol during stress conditions, a process termed ER to CYtosol Signaling (ERCYS) 3. DNAJB12 is essential for triaging arrested membrane protein intermediates, such as N1303K-CFTR, for endoplasmic reticulum-associated autophagy rather than conventional ERAD pathways 2. The protein also responds to mitochondrial stress, with expression regulated by mitochondrial uncouplers like CCCP, and may influence mitochondrial dynamics and PINK1 stabilization 4. Disease relevance includes associations with osteoarthritis 5 and dilated cardiomyopathy risk 6. Additionally, DNAJB12 may play a role in photoreceptor metabolism pathways related to myopia development 7. Overexpression leads to formation of nuclear membrane structures called DJANGOS, suggesting roles in nuclear membrane organization 1.