 A new scalable, efficient, and cost-effective method to accurately and rapidly locate proteins within cells paves the way for an improved understanding of protein and cellular function in the brain. Inside cells, proteins carry out the processes that make life possible. In nerve cells, proteins help the brain process information and store memories by generating action potentials, connecting partner neurons through synapses, and regulating synaptic transmission. But when these proteins stop working properly, the effects can be devastating, in some cases causing neurodegenerative diseases and psychiatric disorders. Because what a protein does strongly depends on where it is located, the ability to accurately locate proteins within cells is a critical step to understanding their function. However, the techniques currently used to locate proteins are time-consuming and often unable to pinpoint proteins or produce good images of them, especially in dense tissue like that of the brain. Because of these limitations, the location of only a small fraction of proteins among the thousands that exist in neurons have been mapped. But a recently developed technique called slender allows researchers to more rapidly and precisely locate proteins even within living brain tissue. The most reliable way to track proteins is to insert the specific DNA sequence for a tag into a gene that encodes a protein of interest. That way, when the protein is produced, it carries the tag and can be easily and accurately tracked. The rise of the popular CRISPR-Cas9 system has provided researchers with genome editing technology to rapidly and efficiently insert tags of this type. CRISPR-Cas9 breaks the DNA of the target gene at a precise location and a normal DNA repair mechanism, called Homology Directed Repair, or HDR, then incorporates the sequence encoding the tag while repairing the break. The use of CRISPR-Cas9 in the brain, however, has been limited by the lack of the HDR mechanism in mature, non-dividing neurons and the inability to efficiently deliver the necessary machinery to the desired cells. Slender, which is short for single-cell labeling of endogenous proteins by CRISPR-Cas9-mediated Homology Directed Repair, overcomes these limitations by applying CRISPR-Cas9 to the immature, dividing cells that generate the mature cells of interest, instead of targeting the mature cells directly. Because the mature cells inherit the CRISPR-Cas9-modified DNA from the dividing cells, they express the tagged protein. To target immature dividing cells, the researchers injected and expressed CRISPR-Cas9 into the brains of mouse embryos as they developed inside their mothers and then applied electrical current. This current formed tiny holes in the young cells, through which the CRISPR-Cas9 components for genome editing could pass. The researchers showed that Slender could be used to label a variety of proteins located in different compartments of cells, in different cell types, and in different regions of mouse brains of various ages. Using electron microscopy, the tagged proteins could be located with nanometer precision. By incorporating two different kinds of tags, Slender could also be used to image two different proteins in a single cell. And by inserting a fluorescent tag such as green fluorescent protein, GFP, Slender even allowed proteins in living brain tissue to be imaged. This capability is important because it can reveal how proteins move and interact with each other in both healthy and diseased tissue. Slender provides the opportunity to determine the location and dynamics of many types of proteins in the brain. Future studies may aim to extend its application to monitoring treatments designed to correct abnormal protein function or localization.