PPIP5K2 is a bifunctional inositol kinase that synthesizes inositol pyrophosphates (PP-InsP5 and (PP)2-InsP4, also called InsP7 and InsP8) by phosphorylating inositol hexakisphosphate and related substrates in concert with IP6K family kinases. These pyrophosphate-containing molecules regulate diverse cellular processes including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling, and neutrophil activation. PPIP5K2 contains a functional nuclear localization signal and can shuttle between cytoplasm and nucleus, where its localization is regulated by phosphorylation at serine 1006, enabling compartmentalized signaling. Clinically, PPIP5K2 mutations cause autosomal recessive nonsyndromic hearing loss (DFNB100); the p.Arg837His variant identified in Pakistani families reduces phosphatase activity while elevating kinase activity, and mice lacking the phosphatase domain exhibit cochlear outer hair cell degeneration 1. Beyond hearing, PPIP5K2 has emerged as a cancer-associated gene. In colorectal cancer, PPIP5K2 promotes cell proliferation and migration independent of its kinase activity by facilitating DNA homologous recombination repair through nuclear translocation and RPA70 recruitment 2. In non-small cell lung cancer, PPIP5K2 drives proliferation and metastasis via the AKT/mTOR signaling pathway 3. In ovarian cancer, a long noncoding RNA stabilizes PPIP5K2 to promote complement C5 secretion and myeloid-derived suppressor cell infiltration 4. Machine learning analysis nominates PPIP5K2 among inositol pathway genes potentially involved in Parkinson's disease pathogenesis 5, and corneal function studies support a role in keratoconus 6.