Ripk1, short for receptor-interacting protein kinase 1, is a key mediator of cell death and inflammation. It functions in coordinating cell survival, inflammation, and immunogenic cell death (ICD) [1]. Ripk1 is involved in pathways such as apoptosis, necroptosis, and inflammatory pathways downstream of death receptors (DRs) and pattern recognition receptors (PRRs) [5]. Genetic models, like KO or CKO mouse models, have been crucial in studying its functions.

In mouse models, RIPK1-deficient mice die soon after birth, highlighting its essential role in development [2]. In the context of diseases, genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK'547 significantly attenuated airway inflammation, remodelling, emphysema, and apoptotic and necroptotic cell death [3]. In ALS, loss of OPTN led to axonal degeneration through engagement of necroptotic machinery including RIPK1, and RIPK1-and RIPK3-mediated axonal pathology was observed in SOD1(G93A) transgenic mice [4].

In conclusion, Ripk1 is vital in regulating cell death and inflammation processes. Mouse models, especially KO/CKO models, have been instrumental in revealing its role in diseases such as COPD and ALS. Targeting Ripk1 shows promise as a therapeutic approach for these and other related diseases [3,4].