The neonatal Fc receptor (FcRn) extends the serum half-life of immunoglobulins G (IgG) through a pH-dependent interaction that protects and recycles IgG during intracellular trafficking. To understand the molecular basis of the prolonged half-life observed with the Fc variant KU-1, this study employs X-ray crystallography and in silico modeling to elucidate the mode of interaction (MOI) between FcRn and KU-1. Deciphering this interaction has the potential to significantly impact the development of KU-1-based biopharmaceuticals, paving the way for enhanced therapeutic efficacy and safety profiles.