Tktl1, or transketolase-like 1, is a crucial regulatory enzyme in the pentose phosphate pathway (PPP), which is involved in energy synthesis [4]. It has been linked to anaerobic glucose metabolism (Warburg effect), a characteristic of cancer cells, and is considered a biomarker for invasive growth, metastasis, and resistance to certain therapies [3].

In the context of human evolution, modern human Tktl1 differs from Neanderthal Tktl1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, it was found that the modern human variant increases the abundance of basal radial glia (bRG), which generate more neocortical neurons than intermediate progenitors (bIPs), suggesting differences in neocortical neurogenesis between modern humans and Neanderthals [1].

In cancer research, knockdown of Tktl1 in THP-1 AML cells impairs hypoxia-induced overexpression of glucose-6-phosphate dehydrogenase (G6PD) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), affecting the redox capacity of NADPH-and NADH-related cells and the metabolic adaptation to hypoxia [2]. In ovarian cancer cells, inhibiting Tktl1 re-sensitizes paclitaxel-resistant cells to paclitaxel, reducing cell proliferation, increasing ROS levels and apoptosis [5]. In cervical cancer cells, interference of Tktl1 expression inhibits cell proliferation, invasion, migration, and glycolysis [6].

In conclusion, Tktl1 plays essential roles in both normal biological processes like neocortical neurogenesis and in disease-related processes such as cancer metabolism. Gene knockout models, including those in mouse neocortex and human cancer cell lines, have been instrumental in revealing these functions. These findings enhance our understanding of the biological importance of Tktl1 in evolution-related neurogenesis and in cancer-associated metabolic reprogramming.