Neuroinflammation has been implicated in a diverse array of degenerative conditions, ranging from Multiple Sclerosis to Alzheimer’s disease. Dr. Gros and team previously uncovered genes that can prevent neuroinflammation and provide new opportunities for drug discovery for a variety of clinical indications. Here, they propose to specifically inhibit the ubiquitin-specific protease 15 (USP15), in view of managing and treating neuroinflammation. This project will expand the therapeutic field for USP15, map out USP15 pathways and associated partners in immune cells, better understand the functional role of USP15 in brain and in immune cells during neuroinflammation and pursue the development and validation of small molecule USP15 inhibitors. The whole project will build value through identification of small molecule leads for modulating USP15 for neuroinflammation and bring it closer to the clinic.