This lecture delves into the interrogation of the local proteome at subcellular and single-cell levels, focusing on chemical actionability and responsivity for functional signaling. It covers technologies like APEX/APEX2 for spatial proteomics target identification and the challenges of mapping spatiotemporal reactivity in intact living systems. The instructor discusses precision electrophile delivery concepts, the Halo Tag system, and the G-REX/T-REX tandem tool for function-guided profiling. The lecture emphasizes the importance of understanding the precision electrophile responsivity of the cysteome in guiding precision medicine and drug discovery.