HSPA8 is a constitutively expressed molecular chaperone that performs diverse cellular functions through ATP-dependent conformational changes 1. Its primary function involves protein quality control, including folding of newly synthesized proteins, refolding of misfolded proteins, and targeting proteins for degradation 1. The protein operates through cycles of ATP binding, hydrolysis, and ADP release, with co-chaperones regulating substrate specificity and fate decisions between folding and degradation pathways. HSPA8 plays a critical role in chaperone-mediated autophagy by recognizing proteins containing KFERQ motifs and facilitating their lysosomal degradation. Beyond protein homeostasis, HSPA8 functions as an 'amyloidase' that disassembles functional RHIM-containing amyloids to suppress necroptosis signaling 2. The protein also regulates ferroptosis, a form of iron-dependent cell death, by modulating SLC7A11/GPX4 signaling pathways 34. In disease contexts, HSPA8 demonstrates dual roles: it can promote cancer progression by suppressing ferroptosis in hepatocellular carcinoma and cholangiocarcinoma 35, while also participating in innate immune responses through interaction with DNA-PK pathways 6. Additionally, HSPA8 contributes to cardiovascular pathology, with expression changes associated with myocardial ischemia-reperfusion injury 7 and diabetic kidney disease through SREBP regulation 8.