Ppp6r3, a regulatory subunit of protein phosphatase 6 (PP6), is involved in multiple biological processes. PP6 plays a role in innate immunity, cell survival, and cellular homeostasis. The PP6 complex has been shown to be crucial in the activation of RIPK1-dependent PANoptosis, a unique innate immune inflammatory lytic cell death pathway [2].

In a study on bone mineral density (BMD), Ppp6r3 deletion in mice decreased BMD, indicating its potential role in regulating BMD [5]. Additionally, in nodular fasciitis, a mesenchymal neoplasia, the amplification of the novel PPPR6-USP6 gene fusion, involving Ppp6r3, led to USP6 mRNA transcriptional upregulation, suggesting an oncogenic role [1,3]. Also, Ppp6r3 was identified as one of the genes in fusions in various cancers like breast cancer (PPP6R3-TENM4-NRG1) and serous ovarian carcinoma (DPP9-PPP6R3), and in myoepithelioma-like tumor of the vulvar region (PPP6R3::FHDC1), potentially playing a role in tumorigenesis [4,6,7]. It was also found to interact with the influenza A virus RNA-dependent RNA polymerase, with knockdown of PP6 catalytic subunit reducing viral RNA accumulation, indicating its role in virus replication [8].

In summary, Ppp6r3 is involved in diverse biological functions including cell death regulation, bone mineral density regulation, and potentially in tumorigenesis and viral replication. Studies using gene knockout models in mice have been valuable in revealing its role in BMD regulation. Its involvement in various disease-related processes like cancer and viral infection shows its importance in understanding disease mechanisms.