RNA-binding proteins (RBPs) are key regulators of translation and have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Among candidate pathological entities are heterogeneous co-aggregates, or “MetaAggregates,” composed of amyloids, RBPs, and RNA G-quadruplexes (rG4s). To explore their molecular constituents, we developed a proteomic approach using a psoralen-conjugated RBP to crosslink with a biotinylated rG4, enabling isolation of MetaAggregates from ALS brain extracts. Single-cell RNA-seq of ALS iPS-derived neurons identified ELAVL4 as a cytoplasmic RNA-binding protein and revealed enrichment of an IGFBP2-derived rG4 structure in ALS-specific neurons. Label-free LC-MS/MS and amyloidogenicity-based principal component analysis revealed 79 candidate proteins with roles in RNA processing, metabolism, trafficking, and stress responses.