C1ql1, also known as CTRP14, is a member of the C1q/tumor-necrosis-factor-related protein (CTRP) family. It is a secreted protein highly conserved in mammals, expressed in various tissues such as the brain, adipose tissues, ovaries, cochlea, and more. In the nervous system, it interacts with BAI3/ADGRB3 and is involved in synapse formation and maintenance. It may also regulate angiogenesis of endothelial cells through the ERK1/2 signal pathway [2,6].

In ApoE-deficient mice, overexpression of C1QL1 showed no significant difference in atherosclerotic plaque area, indicating that C1QL1 is largely dispensable for atherosclerosis formation [1]. In the cochlea, C1ql1-null mice exhibited progressive hearing loss with reduced nerve fibers innervating hair cells, suggesting it is essential for hair cell innervation and outer hair cell survival [5]. In the ovary, blockade of C1QL1 in prepubertal mice impaired folliculogenesis and depleted the ovarian follicle reserve [3]. In oligodendrocyte progenitor cells (OPCs), C1QL1 deficiency reduced OPC differentiation into oligodendrocytes and myelin production, while over-expression had the opposite effect [4].

In conclusion, C1ql1 plays crucial roles in multiple biological processes including synapse formation, angiogenesis, hearing, ovarian folliculogenesis, and oligodendrocyte differentiation. Gene-knockout mouse models have been instrumental in revealing these functions, especially in understanding its role in diseases related to these processes such as atherosclerosis, hearing loss, and ovarian function decline.