HSD17B2 is a NAD-dependent oxidoreductase that catalyzes the inactivation of potent steroid hormones, converting estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5α-androstan-3,17-dione [UniProt Function]. This enzymatic activity is crucial for regulating steroid hormone bioavailability and has broad implications across multiple pathological conditions. In prostate cancer, HSD17B2 functions as a tumor suppressor. Expression is progressively reduced during cancer development 1, and HSD17B2 overexpression suppresses androgen-induced cell proliferation and xenograft growth 1. Conversely, HSD17B2 expression in cancer-associated fibroblasts paradoxically promotes castration-resistant prostate cancer progression through AR/ITGBL1 axis activation 2, suggesting context-dependent roles depending on cellular compartmentalization. In colorectal cancer, HSD17B2 is consistently downregulated and acts as a novel tumor-suppressive regulator; ectopic expression significantly suppresses cellular proliferation 3. Regarding reproductive health, HSD17B2 dysregulation contributes to endometriosis pathogenesis. Epithelial-mesenchymal transition (EMT) suppresses HSD17B2 expression through TGF-β/Snail signaling, disrupting estradiol metabolism 4. Menstrual blood HSD17B2 expression shows diagnostic potential for endometriosis discrimination 5. Additionally, downregulated HSD17B2 protein levels in recurrent implantation failure endometrium suggest impaired receptivity 6. HSD17B2 genetic variants are also associated with uterine leiomyoma risk 7.