Ppp1r9b, also known as SPINOPHILIN or NEURABIN-2, is a multifunctional protein and a regulatory subunit of protein phosphatase 1 (PP1). It plays a crucial role in regulating protein-protein interactions across different cell signaling pathways. It is involved in cell cycle regulation through its association with PP1 in dephosphorylating the retinoblastoma protein (pRB), and also has functions related to cytoskeletal regulation [1,2,3].

In cancer research, loss-of-function studies have shown significance. In breast tumors, downregulation of Ppp1r9b increases the cancer stem cell population, contributing to a more malignant phenotype and poor prognosis [4]. In lung tumors, its down-regulation, potentially due to over-expression of miRNA106a* targeting it, contributes to tumorigenesis [5]. In colon carcinoma, lower Ppp1r9b expression levels are associated with a more aggressive histologic phenotype, faster relapse, and poorer survival, as well as chemoresistance [6]. An oncogenic mutation of Ppp1r9b (SPN-A566V) found in human tumors promotes tumorigenic and stemness properties in cells with mutant p53 [1].

In conclusion, Ppp1r9b is essential for normal cell function, especially in cell cycle regulation and cytoskeletal organization. Model-based research, especially in cancer models, has revealed its tumor-suppressive role. Its loss or mutation can lead to increased tumorigenicity, stemness properties, and poor patient prognosis in various cancers, highlighting its importance as a potential target for cancer therapy [1,4,5,6].