The G-Protein Coupled Receptor Kinase 2 (GRK2) Orchestrates Hair Follicle Homeostasis

The study reveals that G protein-coupled receptor kinase 2 (GRK2) is crucial for maintaining hair follicle (HF) homeostasis. Using a keratinocyte-specific knockout mouse model, researchers found that the absence of epidermal GRK2 leads to early changes in the hair germ region, abnormal anagen phase induction, and the formation of cyst-like structures in place of normal HFs. These cysts exhibit abnormal growth and differentiation, do not undergo the typical catagen phase, and resemble abortive HFs that fail to develop proper anagen cell layers. The cysts caused by GRK2 deletion displace the dermal papilla, disrupt hair follicle stem cell architecture, and ultimately result in bulge destruction and hair loss. Over time, these epidermal cysts in GRK2 knockout mice show destruction patterns similar to those seen in alopecia areata, suggesting a link between GRK2 function, cyst formation, and hair loss mechanisms, including those in immune-mediated alopecias.