Necroptosis is a necrotic programmed cell death mediated by the RIPK1-RIPK3-MLKL signaling cascade downstream of death receptors such as TNFR, Fas and TRAIL. Many neuroinflammatory diseases, including multiple slerosis, ALS, and Alzheimer's disease have been linked to activation of necroptosis. In their study published in Molecular Cell, the Yuan Lab identifies the TAM receptor tyrosine kinase family (Tyro3, Axl, Mer) as novel promoters of necroptosis. TAM kinases regulate the ultimate step in the necroptosis signaling, namely the oligomerization of MLKL, which  results in the formation of a transmembrane pore and cell membrane rupture, driving the necrotic cell death. Both knockout and inhibition of TAM kinases protect mice from TNF-induced systemic inflammatory response syndrome.  This study discovers a novel and unexpected role for the anti-apoptotic, oncogenic, and anti-inflammatory TAM kinases as promoters of the pro-inflammatory necroptosis, shedding light on the biological complexity of regulation of inflammation.