Macf1, also known as actin crosslinking factor 7 (ACF7), is a member of the spectraplakin family. As a large protein scaffold over 700 kDa, it coordinates crosstalk between actin microfilaments and microtubules, essential for processes like cell-cell connections, cell polarity, vesicular transport, proliferation, and cell migration. It participates in signaling pathways such as Wnt/β-catenin and GSK-3 [2,3,4].

Knockout mouse models have been crucial in revealing Macf1's roles. In embryo development, its loss-of-function affects multiple tissues [1]. In bone, conditional knockout (cKO) of Macf1 in mesenchymal stem cells leads to decreased osteogenic differentiation, ossification retardation in early development, and attenuated bone mass and formation in adulthood. Macf1 promotes osteoblast differentiation by sequestering repressors in the cytoplasm, enhances osteoblastic cell migration through regulating MAP1B via the GSK3β/TCF7 pathway, and mediates preosteoblast migration by promoting focal adhesion turnover through EB1 [5,6,7]. Also, Macf1 overexpression in bone marrow-derived mesenchymal stem cells (BMSCs) alleviates senile osteoporosis in mice through the TCF4/miR-335-5p signaling pathway [8]. In the nervous system, genetic mutation or dysregulation of Macf1 is associated with neurodevelopmental and neurodegenerative diseases [2].

In conclusion, Macf1 is essential for maintaining normal functions in many tissues, playing key roles in embryo development, neural development, and bone formation. The use of KO/CKO mouse models has significantly enhanced our understanding of its functions and its implications in diseases such as osteoporosis and neurological disorders.