NEIL1 (nei like DNA glycosylase 1) functions as a DNA glycosylase in the base excision repair (BER) pathway, recognizing and removing oxidatively damaged bases from both nuclear and mitochondrial DNA 1. The enzyme exhibits preferential activity toward oxidized pyrimidines including thymine glycol, formamidopyrimidines (Fapy), and 5-hydroxyuracil, with additional AP lyase activity that introduces single-strand breaks through beta-delta elimination 2. NEIL1 demonstrates unique replication-associated repair functions, being preferentially activated during S-phase and showing enhanced activity on double-stranded DNA substrates, including damage upstream of replication forks 3. The protein physically interacts with flap endonuclease 1 (FEN-1), enabling participation in long-patch BER during DNA replication 4. NEIL1 also processes complex lesions including psoralen-induced DNA-DNA cross-links in multi-stranded DNA structures 5. Deficiency in NEIL1 function significantly increases cancer susceptibility, as demonstrated in Neil1 knockout mice showing >3-fold increased susceptibility to aflatoxin B1-induced carcinogenesis 2. The gene's importance extends to age-related diseases, with deficiencies linked to metabolic syndrome, neurodegeneration, and Alzheimer's disease 6, highlighting its critical role in maintaining genomic integrity and human health.