We found that VPS33B and VIPAR deficiencies result in a reduction of LH3-dependent post-translational modification of collagen IV in these cells accompanied by an abnormal deposition of the extracellular matrix (ECM) and disruption of cell polarity in three-dimensional (3D) cyst models of VPS33B, VIPAR, and LH3 kd cells. Here, PLOD3 is linked to cyst.