C1ql1, also known as CTRP14, is a member of the C1q/tumor-necrosis-factor-related protein (CTRP) family. It is a secreted protein that is highly conserved in mammals and is expressed in various tissues such as the brain, adipose tissues, cochlea, ovary, and more. In the body, it is involved in multiple biological processes, like synapse formation and maintenance, and may be associated with pathways related to angiogenesis and cell-cell interactions [2,8].

In ApoE-deficient mice, overexpressing C1ql1 had no significant impact on atherosclerotic plaque formation, suggesting it is largely dispensable for this process [1]. In the brain, studies using a C1ql1-Cre knockin mouse model have shown that C1ql1 expressed in inferior olivary neurons interacts with BAI3/ADGRB3 and controls synapse formation and maintenance in cerebellar Purkinje cells. Also, in mature Purkinje cells, C1ql1-Bai3 signaling, coordinated with neuronal activity, is necessary for climbing fiber synapse formation [2,4].

In the cochlea, C1ql1 is expressed in adult outer hair cells in a tonotopic gradient. Deletion of C1ql1 in mice causes progressive hearing loss, reduction in the number of nerve fibers innervating hair cells, and significant outer hair cell loss, indicating its essential role in hair cell innervation and outer hair cell survival [3,7].

In the ovary, deficiency of C1ql1 in mice leads to depletion of the ovarian follicle reserve through intra-ovarian and endocrine control, as it affects folliculogenesis, granulosa cell apoptosis, and autophagy [5].

In oligodendrocyte progenitor cells (OPCs), C1ql1 deficiency reduces the differentiation of OPCs into oligodendrocytes and myelin production, while over-expression has the opposite effect, suggesting C1ql1 may initiate a signaling pathway for OPC differentiation [6].

In conclusion, C1ql1 plays diverse and important roles in multiple biological processes, including synapse formation in the brain, hair cell innervation and survival in the cochlea, ovarian folliculogenesis, and oligodendrocyte differentiation. Gene-knockout mouse models have been crucial in revealing these functions, providing insights into potential mechanisms underlying diseases related to these processes, such as hearing loss, ovarian aging, and demyelinating diseases.