PPIP5K2, a diphosphoinositol pentakisphosphate kinase, is involved in interconverting 5-IP7 and IP8, key members of the inositol pyrophosphate cell-signaling family. Its actions at the interface of cell signaling and bioenergetic homeostasis impact many biological processes [4].

In gene-trap mouse models, irregular corneal surfaces and pathological corneal thinning resembling keratoconus were observed, indicating its role in normal corneal function and keratoconus pathogenesis [2]. Mice homozygous for a targeted deletion of the Ppip5k2 phosphatase domain exhibit degeneration of cochlear outer hair cells and elevated hearing thresholds, suggesting its role in hearing [4]. In NSCLC, knockdown of PPIP5K2 significantly inhibits the phosphorylation of the AKT/mTOR signaling pathway, affecting cell proliferation and metastasis [3]. In CRC, S1006 dephosphorylation of PPIP5K2 promotes its nuclear translocation, facilitating DNA homologous recombination repair and enhancing cell survival [1].

In conclusion, PPIP5K2 is crucial in multiple biological processes and disease conditions. Gene-knockout mouse models have been instrumental in revealing its role in diseases such as keratoconus, hearing loss, NSCLC, and CRC. Understanding PPIP5K2's functions provides potential therapeutic targets for these diseases.