Receptor-interacting protein kinase 3: A macromolecule with multiple cellular actions and its perspective in the diagnosis and treatment of heart disease.

Receptor-interacting protein kinase 3 (RIP3), a serine/threonine kinase of the RIP family, has emerged as a critical regulator of necroptosis, a necrosis-like form of cell demise. However, recent research has revealed that overactivated RIP3 might also be involved in the regulation of other cell death forms, such as pyroptosis, autophagy, mitochondrial permeability transition pore (mPTP)-necrosis and ferroptosis, and operates in diverse cellular compartments. RIP3 can therefore affect inflammation, oxidative stress and energy metabolism, further underscoring its pivotal role in cellular homeostasis. Furthermore, elevated circulating levels of RIP3 have been observed in cardiac disorders such as heart failure, myocardial infarction, and coronary artery disease and might correlate with disease severity and worse prognostic outcomes. On the contrary, the pharmacological inhibition of RIP3 has shown protective effects due to complex mechanisms involving necroptosis retardation, prevention of immune cell infiltration, and mitigation of cardiac cells mitochondrial damage. A detailed understanding of the complexity of RIP3's function in the heart may favour its diagnostic potential and lead to the development of future therapeutic interventions.