Citrin is a mitochondrial calcium-binding aspartate/ glutamate carrier (AGC) protein that plays an important role in the urea cycle and other metabolic processes. Citrin deficiency consists of two distinct phenotypes: Adult Onset Type II Citrullinemia (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD), which are autosomal recessive. In recent years, there have been many advances in research on the clinical manifestations, diagnostic methods, pathogenesis and treatment of Citrin deficiency, and the pathophysiological mechanisms of its development are reviewed below. In 2001, Ohura et al. identified a mutation in the SLC25A13 gene in children with intrahepatic cholestasis with hyperammonemia and galactosemia, and defined the disease as neonatal intrahepatic cholestasis due to Citrin deficiency [4]. In addition to galactosemia, hypoproteinemia, hemorrhagic tendencies, hypoglycemia, and markedly elevated methemoglobin, there may be elevations of various amino acids such as citrulline, methionine, phenylalanine, and threonine [5]. Early detection of elevated citrulline is important to confirm the diagnosis, but not all patients with NICCD have elevated citrulline. Recent studies have found that children with NICCD have a “Chubby Face” and a significantly higher facial fullness index than normal children of the same age, suggesting that their facial features can also be used as a reference diagnostic indicator [7]. The diagnosis of NICCD can only be confirmed by genetic diagnosis or Citrin immunohybridization of lymphocytes and skin fibroblasts. Some children with NICCD still have non-specific symptoms such as fatigue, a few have pancreatitis, hyperlipidemia and seizures, and from the age of 2 years have a tendency to eat beans, peanuts, etc., and an aversion to sweets and cereals. Citrin deficiency is a genetic metabolic disorder with a high incidence, especially in East Asia. Some children with NICCD have an atypical presentation, such as undetectable elevation of blood citrulline, and the final diagnosis is difficult to be confirmed by biochemical parameters, while genetic diagnosis is an effective test for Citrin deficiency and deserves to be promoted. The pathogenesis remains to be further elucidated, and most treatments are limited to symptomatic management. Public awareness of the disease, early detection and timely treatment, long-term follow-up of patients, and further clarification of its pathogenesis and progression mechanisms should be strengthened.