RIP protein refers to the Receptor-interacting protein kinase family, which consists of seven Serine/Threonine kinases that play a key role in cell survival and cell death signaling. Each member of the RIP family contains a conserved kinase domain and other domains that determine the specific kinase function through protein-protein interactions. RIP1 and RIP3 are particularly well-known for their critical roles in necroptosis, a programmed necrosis and a non-apoptotic inflammatory cell death process. Dysregulation of RIP kinases contributes to a variety of pathogenic conditions such as inflammatory diseases, neurological diseases, and cancer. RIP kinases participate in different biological processes, including those in innate immunity, but their downstream substrates are largely unknown. They are known to be involved in various cellular signaling pathways leading to the activation of MAPKs and NF-κB, as well as cell death. RIP1 is a key mediator of several signaling pathways, and RIP2 is critical for signaling from NOD-like receptors and can trigger MAPKs and NF-κB activation. The role of RIP3 is major in the induction of necrosis, and it may participate in the process of apoptosis and regulate NF-κB signaling.