PCLAF, also known as PAF15 or KIAA0101, is a cell-cycle regulated protein. It regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass via interaction with PCNA [4]. It is involved in multiple pathways such as the AKT/mTOR signaling, TGF-β signaling, and the E2F1/PTTG1 axis, and is important in various biological processes including cell proliferation, cell cycle progression, cell fate changes, and senescence [1,2,3].

Genetic deletion of PCLAF in macrophages inhibited bone marrow adipocyte (BMAd) senescence and delayed skeletal aging. This indicates that PCLAF is an inducer of BMAd senescence, which in turn contributes to skeletal aging. In the lung, genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis, suggesting PCLAF-DREAM complex is crucial for alveolar cell plasticity and lung regeneration [1,2]. Knocking down PCLAF restricted the proliferation of neuroblastoma cells in vitro and in vivo, as PCLAF accelerates the G1/S transition of the neuroblastoma cell cycle by activating the E2F1/PTTG1 signaling pathway [3].

In conclusion, PCLAF plays essential roles in cell-related biological processes. Its gene knockout or knockdown in mouse models has revealed its contributions to diseases like age-related osteoporosis, lung fibrosis, and neuroblastoma, providing potential therapeutic targets for these conditions.