Tyro3, Axl and MerTK, which constitute the TAM family of receptor tyrosine kinases, are key regulators of homeostasis in many tissues, including the CNS. Although much is known about the receptors’ functions, little is known about their ligands, PROS1 and GAS6, and how they contribute to TAM functional diversity in the CNS and elsewhere. PROS1 and GAS6 are considered homologous ligands with overlapping functions, but our preliminary studies indicate they are not functionally interchangeable, even within the same cells, despite signaling through the same receptor, MerTK. This perplexing finding calls for deciphering the molecular pathways instigated by PROS1 versus GAS6 through MERTK, affecting neurogenesis, inflammation and debris removal – all necessary to maintain CNS homeostasis and enable tissue repair following injury.  Here, we focus on microglia, the resident immune cells of the brain, to tease apart the molecular diversity of PROS1 versus GAS6 in CNS homeostasis and following retinal injury. This proposal brings together the expertise of Inbal Benhar in harnessing RNA-seq as a platform to discover neuro-immunological pathways in retinal injury, together with those of Tal Burstyn-Cohen in TAM signaling in the brain and retina, who has developed unique mouse models to study these questions.