Neurons differentiated from iPSCs tend to have an immature phenotype, which can impact cellular functions critical to the successful modeling of prion-like protein propagation and seeding (a, b). New techniques such as brain organoids (c), microfluidic devices (d) and CRISPR/Cas9 gene editing (e) are important tools to overcome these limitations and further establish iPSCs as a model of choice to study the properties and role of prion-like proteins in neurodegenerative diseases. Cas9 CRISPR associated protein 9, CRISPR Clustered Regularly Interspaced Short Palindromic Repeats, Pop. 1 population 1, Pop. 2 population 2, Pop. 3 population 3, 3D three-dimensional.