Mitotic homologous recombination (HR) is a crucial pathway for precise DNA repair, maintaining genomic stability and suppressing tumorigenesis. HR repairs DNA double-strand breaks (DSBs) and other lesions, protecting cells from death and mutagenesis. Mutations in HR genes, such as BRCA1, BRCA2, and PALB2, lead to developmental abnormalities and cancer. HR involves strand exchange catalyzed by RAD51, which forms nucleoprotein filaments with single-stranded DNA (ssDNA). End resection, where ssDNA is generated from DSB ends, is a key step in HR. RAD51 filaments invade the ssDNA, and strand exchange occurs, leading to precise repair using the sister chromatid as a template. HR deficiency results in error-prone repair pathways like non-homologous end joining (NHEJ) and single-strand annealing (SSA), contributing to genome instability. HR proteins like BRCA1 and BRCA2 are tumor suppressors, and defects in HR pathways are associated with human diseases, including cancer and aging. The review discusses the roles of key HR proteins, recent advances in understanding HR mechanisms, and the distinct phenotypes associated with inherited mutations in HR genes.Mitotic homologous recombination (HR) is a crucial pathway for precise DNA repair, maintaining genomic stability and suppressing tumorigenesis. HR repairs DNA double-strand breaks (DSBs) and other lesions, protecting cells from death and mutagenesis. Mutations in HR genes, such as BRCA1, BRCA2, and PALB2, lead to developmental abnormalities and cancer. HR involves strand exchange catalyzed by RAD51, which forms nucleoprotein filaments with single-stranded DNA (ssDNA). End resection, where ssDNA is generated from DSB ends, is a key step in HR. RAD51 filaments invade the ssDNA, and strand exchange occurs, leading to precise repair using the sister chromatid as a template. HR deficiency results in error-prone repair pathways like non-homologous end joining (NHEJ) and single-strand annealing (SSA), contributing to genome instability. HR proteins like BRCA1 and BRCA2 are tumor suppressors, and defects in HR pathways are associated with human diseases, including cancer and aging. The review discusses the roles of key HR proteins, recent advances in understanding HR mechanisms, and the distinct phenotypes associated with inherited mutations in HR genes.