An orphan disease is chronically debilitating, severe, life-threatening, and prevalence of less than 1 per 5,000 people. Congenital leptin deficiency is one of those diseases, which affects few people, but demands a costly treatment. Currently, the disease is effectively treated with recombinant leptin obtained through biotechnological genetic engineering processes; however, it is not produced in Colombia. This project aims to develop a genetically modified organism capable of heterologously expressing the hormone leptin. Although the project is in its initial stages, some results have been obtained. The leptin gene in silico design was achieved, considering the preferential codons used for Pichia pastoris. The leptin was synthesized and introduced into a cloning plasmid, then amplified and digested with xhoI and notI enzymes. The obtained insert (leptin gene and cohesive sites) was ligated within the expression plasmid pPICZ-alpha –digested with the same enzymes–. Afterward, we obtained the plasmid pPICZ-alpha-leptin, used to transform E. coli XL1Blue. Some colonies were evaluated by colony PCR to verify the leptin gene presence. One positive colony was amplified to purify its plasmid and sequencing. We transformed P. pastoris GS115(Mut+) with this corroborated plasmid, obtaining a recombinant yeast grown in BMGY and induced in BMMY media. Recombinant leptin was purified from the supernatant by Ni-resin (8µg/µL). SDS-PAGE analysis confirmed the expression and integrity of a unique ~16kDa band corresponding to leptin. We still need to optimize the culture conditions, and leptin production could be used as a medical treatment for rare diseases.