PRUNE2 (prune homolog 2 with BCH domain) functions as a tumor suppressor gene with critical roles in cancer development and progression. The gene acts as a prostate cancer suppressor regulated by the intronic long non-coding RNA PCA3 through a unique mechanism involving ADAR-dependent RNA editing 1. PRUNE2 expression suppresses cell proliferation, while its silencing increases proliferation in prostate cancer cells 1. The PCA3/PRUNE2 regulatory axis operates as an early molecular event in prostate tumorigenesis, characterized by PCA3 upregulation and PRUNE2 downregulation across tumor grades and stages 2. MicroRNAs miR-19a and miR-421 regulate this axis by targeting PCA3, thereby restoring PRUNE2 tumor suppressor activity and promoting apoptosis in prostate cancer cells 3. Beyond prostate cancer, germline pathogenic variants in PRUNE2 represent a novel prostate cancer predisposition factor, identified in 2.8% of early-onset/familial prostate cancer patients 4. PRUNE2 also shows disease relevance in parathyroid carcinoma and colorectal cancer, where transcription factor FOXF2 directly targets PRUNE2 to suppress cell proliferation and invasion 5. Additionally, Olfaxin, an isoform of PRUNE2, plays a role in olfactory memory and odor preference 6.