Kndc1, also known as kinase noncatalytic C-lobe domain containing 1 and very-KIND/KIAA1768, is a brain-specific Ras guanine nucleotide exchange factor. It negatively regulates dendrite growth in neurons, especially in cerebellar granule cells, and is crucial for proper excitatory synaptic connections and motor coordination [4].

In ovarian cancer, knockdown of Kndc1 enhanced the proliferation of ovarian cancer cells in vitro and in vivo via induction of ERK1/2 phosphorylation, suggesting it may function as a tumor suppressor by suppressing ERK1/2 activity and hindering the malignant transformation of borderline ovarian tumors [1]. In human umbilical vein endothelial cells (HUVECs), knockdown of Kndc1 promoted cell proliferation, reversed cellular senescence and cell cycle arrest in the G0/G1 phase, and enhanced capillary tube network formation. This was achieved via the extracellular signal-regulated kinase signaling pathway and by inhibiting the p53-p21-p16 transduction cascade [2]. Overexpression of Kndc1 in HUVECs possibly inhibited cell activity and function and promoted senescence by triggering a p53-ROS positive feedback loop [3].

In conclusion, Kndc1 plays important roles in multiple biological processes. Its functions in negatively regulating dendrite growth and synaptic connections in the brain are well-established. In addition, through gene knockdown and overexpression models, it has been shown to have implications in cancer proliferation and cellular senescence, providing insights into potential therapeutic targets for ovarian cancer and anti-aging research.