TKTL1 (transketolase-like 1) is a functional transketolase enzyme that plays crucial roles in neurogenesis and metabolic regulation 1. The protein demonstrates authentic transketolase activity through homology modeling and structural analysis, showing appropriate binding sites for thiamine pyrophosphate cofactor and substrate accommodation 1. During human neocortical development, TKTL1 is essential for maintaining basal radial glia (bRG) populations, which are neural progenitor cells that undergo asymmetric divisions to generate both self-renewing bRG and neurons 2. The modern human TKTL1 variant, differing from the Neanderthal variant by a single amino acid substitution (lysine-to-arginine), significantly increases bRG abundance through enhanced pentose phosphate pathway activity and fatty acid synthesis 2. TKTL1 functions as a key regulator in the pentose phosphate pathway, contributing to cellular energy synthesis and metabolic adaptation 3. In cancer contexts, TKTL1 promotes cell survival under hypoxic conditions and contributes to radioresistance by modulating glucose metabolism and reactive oxygen species levels 4. The protein also participates in cell cycle regulation through ribose-5-phosphate binding, facilitating the transition from G1 to S phase 5. However, endogenous TKTL1 expression appears limited in many cell types, with significant expression primarily observed in specific contexts such as germ cells and certain cancer types 6.