Orphan drugs are medications that are created to treat rare diseases, often with limited therapeutic options for specific groups of people. This article reviews orphan drugs, highlighting their significance in addressing treatment gaps for rare diseases, and the supportive policies that promote their development. It includes a list of key orphan drugs and discusses rare diseases that lack sufficient treatments, focusing on leishmaniasis, trypanosomiasis, lymphatic filariasis, phenylketonuria, and cystic fibrosis. For each of these diseases, a variety of approved or investigational orphan drugs are showcased, along with descriptions of their clinical applications and existing constraints. The article delves into the regulatory frameworks created to promote the advancement of orphan drugs. It explores how health authorities, such as the FDA, foster innovation in the industry while guaranteeing drug safety and efficacy by offering incentives such as expedited approvals and financial assistance. Despite these initiatives, challenges such as high costs, limited market incentives, and access barriers continue to persist. To tackle these concerns, the article proposes measures to enhance affordability, accessibility, and international collaboration. The conclusion highlights the importance of ongoing endeavors to address treatment disparities in rare diseases. Future perspectives are further explored in the article, with emphasis on how advances in research and technology, as well as policy, can expedite the creation of orphan drugs while enhancing regulatory mechanisms and making these therapies more accessible to patients.

The sodium dependent SLC13 family transporters comprise of the five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them the three NaDC1, NaDC3 and NaCT are sodium dependent transporters such as di-carboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, the information to the structures is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these receptors and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of the citrate present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporter are required for the development of citrate inhibitors. In this review the structure, function, and regulation of the NaCT receptors are discussed. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT receptors are succinctly summarized.