KEY POINTS: Piezo channels, known for detecting mechanical pressure, were found to be expressed at the lacuna channel membranes of nephrocytes. Piezo loss of function caused nephrocyte dysfunction, including disrupted slit diaphragm structure and altered lacuna channel morphology. Piezo deficiency led to internalized slit diaphragm proteins, reduced autophagy, increased endoplasmic reticulum stress, and impaired calcium homeostasis. BACKGROUND: The METHODS: We used CONCLUSIONS: Together, our findings suggest that Piezo plays an important role in the calcium homeostasis of nephrocytes and is required for maintaining nephrocyte function and the slit diaphragm filtration structure.