RNA extraction is a critical step for downstream applications such as RT-qPCR and RNA sequencing. This method is particularly useful for sensitive cell types and disease models, where the cell integrity may be compromised and cannot sustain any additional steps of cell isolation. Herein, we have developed a simple protocol to extract high quality and purity RNA from a RASTRUM™ advanced cell models using Promega ReliaPrep™ System, fulfilling the requirement RT-qPCR or RNA sequencing downstream analysis.