Long non-coding RNAs (lncRNAs) are a class of transcripts with lengths exceeding 200 nucleotides that do not encode proteins. Despite their crucial roles in cellular functions and biological processes, only a minority of the over 20,000 annotated lncRNAs have been functionally characterized. Here, we established a high-throughput, CRISPR-Interference (CRISPRi) arrayed screening plaKorm with serial cellular and molecular phenotyping to systematically characterize lncRNA functions. We reasoned that the integration of a comprehensive cellular and molecular phenotype can increase the probability of uncovering cellular functions and pathways controlled by lncRNA transcripts.