Knl1, also known as CASC5 and D40, is an evolutionarily conserved kinetochore-associated protein essential for accurate chromosome segregation in eukaryotic cells [2]. It is involved in diverse mitotic processes such as kinetochore assembly, chromosome congression, and mitotic checkpoint signaling [2]. The Knl1-Mis12-Ndc80 (KMN) network, of which Knl1 is a part, is crucial for genomic stability [3].

Mutations in the Knl1 gene cause autosomal recessive primary microcephaly (MCPH4), indicating its critical role in brain growth [1]. In maize, depletion of Knl1 transcript leads to defective cell division during kernel development, demonstrating its conserved role in chromosomal congression and segregation during nuclear division [3]. In cancer research, high expression of Knl1 is associated with poor prognosis in uterine corpus endometrial carcinoma, prostate adenocarcinoma, and colorectal cancer, and knockdown of Knl1 in UCEC and colorectal cancer cell lines inhibits cell proliferation, invasion, and metastasis [4,5,7]. In cardiomyocytes, ATF4 regulates Knl1, increasing cytokinesis during cardiomyocyte proliferation [6].

In summary, Knl1 is essential for mitotic processes and genomic stability. Studies using gene-related models, such as gene knockdown in cells and allele deletion in mice, have revealed its role in diseases like microcephaly and cancer, as well as in cardiomyocyte proliferation. These findings contribute to our understanding of the biological functions of Knl1 and provide potential targets for disease treatment.