FGF homologous factors (FHFs) are the least described group of fibroblast growth factors (FGFs). The FHF subfamily consists of four proteins: FGF11, FGF12, FGF13, and FGF14. Until recently, FHFs were thought to be intracellular, non‐signaling molecules, despite sharing structural and sequence similarities with other members of FGF family that can be secreted and activate cell signaling by interacting with surface receptors. Here, we show that despite lacking a canonical signal peptide for secretion, FHFs are exported to the extracellular space. Furthermore, we propose that their secretion mechanism is similar to the unconventional secretion of FGF2. The secreted FHFs are biologically active and trigger signaling in cells expressing FGF receptors (FGFRs). Using recombinant proteins, we demonstrated their direct binding to FGFR1, resulting in the activation of downstream signaling and the internalization of the FHF‐FGFR1 complex. The effect of receptor activation by FHF proteins is an anti‐apoptotic response of the cell.

Fibroblast growth factors (FGFs) play a key role in lung development by mediating complex interactions between epithelial and mesenchymal cells, which are central to processes such as branching morphogenesis, epithelial differentiation, and alveolarization. The findings regarding this interplay highlight the complexity of FGF signaling, as different FGFs contribute to various aspects of lung formation and maturation. Understanding the role of FGF proteins in shaping the lung is crucial for gaining insight into the biology of its development. Furthermore, FGFs orchestrate complex signaling pathways that regulate lung regeneration in adulthood. Therapeutic strategies targeting FGF-dependent pathways appear promising for repairing and improving lung function in diverse pulmonary diseases. In this review, we describe the current perception of the role of FGF proteins in lung development and regeneration, together with an overview of emerging therapeutic strategies aiming at FGF signaling in lung-related disorders.

Phosphoglycerate mutase (PGAM) is a glycolytic enzyme converting 3-phosphoglycerate to 2-phosphoglycerate, which in mammalian cells is expressed in two isoforms: brain (PGAM1) and muscle (PGAM2). Recently, it was shown that besides its enzymatic function, PGAM2 can be imported to the cell nucleus where it co-localizes with the nucleoli. It was suggested that it functions there to stabilize the nucleolar structure, maintain mRNA expression, and assist in the assembly of new pre-ribosomal subunits. However, the precise mechanism by which the protein translocates to the nucleus is unknown. In this study, we present the first crystal structure of PGAM2, identify the residues involved in the nuclear localization of the protein and propose that PGAM contains a “quaternary nuclear localization sequence (NLS)”, i.e., one that consists of residues from different protein chains. Additionally, we identify potential interaction partners for PGAM2 in the nucleoli and demonstrate that 14-3-3ζ/δ is indeed an interaction partner of PGAM2 in the nucleus. We also present evidence that the insulin/IGF1–PI3K–Akt–mTOR signaling pathway is responsible for the nuclear localization of PGAM2.