Pdgfra, short for platelet-derived growth factor receptor alpha, is a receptor tyrosine-kinase. It plays crucial roles in cell growth, differentiation, and survival by binding to platelet-derived growth factor subunit A (PDGFA). The PDGF-PDGFR signaling pathway is involved in many biological processes, such as embryonic development, tissue repair, and angiogenesis [2].

In the context of diseases, in idiopathic pulmonary fibrosis, single-cell RNA-Seq and lineage tracing in mice showed that Pdgfra+ lipofibroblasts (LipoFBs) in injured lungs acquire fibrogenic pathway activity while retaining their lipogenic identity, potentially contributing to dysregulated repair and fibrosis [1]. In glioblastoma, EPHA2 was found to mediate PDGFA activity along with PDGFRA, and co-upregulation of PDGFRA and EPHA2 led to worse patient prognosis and resistance to PDGFRA inhibitor [2]. In gastrointestinal stromal tumors (GISTs), approximately 90% are driven by activating mutations in KIT or PDGFRA. Imatinib, a first-line treatment, often leads to resistance through secondary mutations in KIT/PDGFRA. Avapritinib, a KIT and PDGFRA inhibitor, shows activity against PDGFRA D842V-mutant GISTs [3,4,6]. Also, in tendon injury, Tppp3+Pdgfra+ cells act as tendon stem cells, and PDGF-AA promotes tenocyte production while Pdgfra inactivation in these cells blocks tendon regeneration. However, Tppp3-Pdgfra+ fibro-adipogenic progenitors can give rise to fibrotic cells, highlighting a challenge in enhancing tendon regeneration without promoting fibrosis [5].

In conclusion, Pdgfra is essential in multiple biological processes and is implicated in various diseases including pulmonary fibrosis, glioblastoma, GISTs, and tendon injuries. Gene-knockout (KO) or conditional-knockout (CKO) mouse models, along with other functional studies, have been crucial in revealing its role in these disease conditions, providing insights for potential therapeutic strategies targeting Pdgfra-related pathways.