GPR34 is a G protein-coupled receptor that functions as a lysophosphatidylserine (LysoPS) sensor, playing critical roles in immune regulation and damage sensing 1. The receptor is primarily expressed on microglia and innate lymphoid cells, where it recognizes LysoPS released by apoptotic or damaged cells 2. Upon LysoPS binding, GPR34 activates downstream PI3K-AKT and ERK signaling pathways, leading to immune cell activation and cytokine production 3. Mechanistically, GPR34 mediates diverse immune functions: ILC3s recognize apoptotic neutrophil-derived LysoPS via GPR34 to produce IL-22 and promote tissue repair 2, while in tumors, LysoPS-GPR34 signaling suppresses ILC1 antitumor activity, functioning as a metabolic immune checkpoint 4. In the central nervous system, myelin debris-derived LysoPS activates microglia through GPR34 to drive neuroinflammation in multiple sclerosis and stroke 3. Similarly, ganglion cell-derived LysoPS activates the microglial GPR34-PI3K-AKT-NINJ1 axis to promote retinal neovascularization in diabetic retinopathy 5. Clinically, GPR34 represents a promising therapeutic target. Genetic or pharmacologic GPR34 inhibition reduces neuroinflammation in demyelination models 3, while selective GPR34 antagonists show efficacy in neuropathic pain 1. Blocking GPR34 on ILC1s or in tumors enhances antitumor immunity 4, suggesting GPR34-targeted approaches warrant clinical development.