HSPBP1 (HSPA binding protein 1) is a cochaperone that regulates Hsp70 chaperone activity through nucleotide exchange factor (NEF) activity 1. Primary function: HSPBP1 inhibits Hsp70-mediated protein folding by preventing ATP binding to the chaperone's nucleotide-binding domain 1, and interferes with STUB1-mediated ubiquitination, thereby protecting misfolded proteins like immature CFTR from degradation. Beyond canonical chaperone regulation, HSPBP1 functions as a stress granule component that promotes their assembly during cellular stress through interactions with G3BP1, HuR, and TIA-1/TIAR proteins 2. HSPBP1 also inhibits formation of cytotoxic Tag7-Hsp70 complexes in serum, potentially protecting normal cells from immune attack 3. Differentially from related NEF BAG-1M, HSPBP1 inhibits steroid receptor activity across glucocorticoid, mineralocorticoid, and androgen receptors 4. Disease relevance: During HIV-1 infection, the virus downregulates HSPBP1 expression through its Tat transactivator, enhancing viral replication 5. Elevated serum HSPBP1 and anti-HSPBP1 antibodies correlate with HIV disease progression and CD4 depletion 6. Clinical significance: HSPBP1 quantification may serve as an adjunctive HIV progression marker 6, complementing established clinical parameters.