The Last Universal Common Ancestor (LUCA) represents an early stage of evolution that can be studied using phylogenetic and bioinformatic methods. Research efforts focus on reconstructing LUCA’s genome, proteome, metabolism, habitat, ecological context, and timeline. A novel method developed by our group identifies structural homologs by comparing protein architectures, defined as the sequential arrangement of homologous domains within a protein. In our approach, proteins are considered homologous if they share identical domain types in the same N-to-C-terminal order. Homologous proteins with the same architecture found in the primary branches of both Bacteria and Archaea are potential candidates for those present in LUCA.