Fkbp1a, also known as FKBP12, is a ubiquitously expressed cis-trans peptidyl-prolyl isomerase. It is involved in multiple biological processes and associated with important signaling pathways such as the mTOR signaling pathway. It has been implicated in the regulation of cell growth, apoptosis, and is also relevant in the context of autophagy [1,2]. Genetic models, like gene knockout (KO) mouse models, have been crucial for studying its functions.

In Fkbp1a-deficient mice, ventricular hypertrabeculation and non-compaction occur. Endothelial cell-restricted ablation of Fkbp1a recapitulated this phenotype, suggesting its role in endocardial regulation of ventricular morphogenesis. Further analysis showed that Fkbp1a is a negative modulator of activated Notch1, with N1ICD upregulated in Fkbp1a-ablated endothelial cells, and overexpression of Fkbp1a reducing N1ICD stability [4]. In the context of glioblastoma, upregulated Fkbp1a protein promotes cell death in U87MG and t98g GBM cell lines via the apoptosis pathway [1]. In HNSCC, its upregulation correlates with poor prognosis and increased metastatic potential [2]. In osteosarcoma, circ_0088212 inhibits progression by regulating the miR-576-5p/FKBP1A axis [3]. In liver hepatocellular carcinoma, high Fkbp1a expression is associated with poor survival, tumor stage, grade, metastasis, and immune cell infiltration [5]. High Fkbp1a expression in white blood cells may serve as a potential screening biomarker for pancreatic cancer [6]. In prostate cancer, circ-PAPPA promotes development through the miR-515-5p/FKBP1A axis [7].

In conclusion, Fkbp1a is essential in regulating ventricular myocardium development through Notch1 modulation. In disease conditions, it plays diverse roles in cancer-related processes such as cell growth, apoptosis, metastasis, and immune infiltration. The use of Fkbp1a KO and conditional knockout (CKO) mouse models has provided valuable insights into its functions in specific biological processes and disease conditions, highlighting its potential as a therapeutic target or biomarker in various diseases.