Hpd, also known as 4-hydroxyphenylpyruvate dioxygenase, is a critical enzyme in tyrosine metabolism. It catalyzes the conversion of 4-hydroxyphenylpyruvate to homogeneous acids in liver tissues [2,3]. This metabolic process is essential for maintaining normal physiological functions, and its disruption can lead to various health issues.

In breast cancer, HPD overexpression is positively correlated with histological grade and clinical stage, and inversely correlated with 10-year overall survival rates, indicating it may be a prognostic predictor and potential therapeutic target [1]. In hepatocellular carcinoma (HCC), HPD mRNA and protein expression are dramatically reduced, and low HPD expression is correlated with larger tumor size, advanced TNM staging, and poor differentiation. Knockdown of HPD increases HCC cell growth and motility, suggesting HPD may serve as a tumor suppressor and prognostic marker for HCC patients [3]. Ttc36-/-mice, which have reduced HPD expression in the liver, exhibit tyrosinemia, damage to hippocampal neurons, and learning and memory deficits, revealing the significance of the TTC36-STK33-PELI1-regulated HPD expression in tyrosinemia and associated neurological disorders [2].

In conclusion, Hpd plays a crucial role in tyrosine metabolism. Its dysregulation is associated with breast cancer and HCC, with implications for prognosis and treatment. The Ttc36-/-mouse model has provided insights into the role of Hpd in tyrosinemia and neurological damage, highlighting the importance of Hpd in maintaining normal physiological functions and its potential as a therapeutic target in related diseases.