Picalm, short for Phosphatidylinositol binding clathrin-assembly protein, is a clathrin-adaptor protein. It plays a critical role in clathrin-mediated endocytosis and autophagy, being involved in pathways related to these processes. Picalm has been associated with various biological processes and diseases, making it an important gene for study. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can help reveal its functions [1,2,4,5].

In a murine tauopathy model, reducing Picalm (by generating Tg30xPicalm+/- mice through crossing Tg30 tau transgenic mice with Picalm-haploinsufficient mice) exacerbated tau pathologies and tau-mediated neurodegeneration. These mice developed more severe motor deficits, had higher pathological tau levels, increased neurofibrillary tangles, and abnormal autophagy markers compared to Tg30 mice, suggesting Picalm expression changes as a risk factor for tau pathology development [5]. Also, genetic depletion of Picalm in a doxorubicin-induced cardiotoxicity mouse model reduced amyloid β-peptide generation, alleviating the cardiotoxicity. In this model, Picalm was upregulated only in cardiomyocytes with doxorubicin-induced cardiotoxicity, and its increase led to higher amyloid β-peptide production and greater cardiomyocyte membrane permeability [3].

In conclusion, Picalm is essential for processes like clathrin-mediated endocytosis and autophagy. Model-based research, especially KO mouse models, has revealed its role in diseases such as Alzheimer's disease-related tauopathies and anthracycline-induced cardiotoxicity. Understanding Picalm's functions through these models provides insights into disease mechanisms and potential therapeutic targets.